Dataset Information

Systemic Investigation Identifying Salivary miR-196b as a Promising Biomarker for Early Detection of Head-Neck Cancer and Oral Precancer Lesions.

ABSTRACT: Liquid biopsy is a rapidly growing field, for it may provide a minimally invasive way to acquire pathological data for personalized medicine. This study developed a systemic strategy to discover an effective salivary biomarker for early detection of patients with head-neck squamous carcinoma (HNSC) and oral precancer lesion (OPC). A total of 10 miRNAs were examined in parallel with multiple independent cohorts. These included a training set of salivary samples from HNSC patients, the TCGA-HNSC and GSE31277 cohorts to differentiate miRNAs between tumor and normal tissues, and groups of salivary samples from healthy individuals, patients with HNSC and OPC. The combined results from the salivary training set and the TCGA-HNSC cohort showed that four miRNAs (miR-148b, miR-155, miR-196b, and miR-31) consistently increased in HNSC patients. Further integration with the GSE31277 cohort, two miRNAs (miR-31 and miR-196b) maintained at high significances. Further assessment showed that salivary miR-196b was a prominent diagnostic biomarker, as it remarkably discriminated between healthy individuals and patients with HNSC (p < 0.0001, AUC = 0.767, OR = 5.64) or OPC (p < 0.0001, AUC = 0.979, OR = 459). Salivary miR-196b could be an excellent biomarker for diagnosing OPC and early detection of HNSC. This molecule may be used for early screening high-risk groups of HNSC.

SUBMITTER: Cheng AJ

PROVIDER: S-EPMC8392418 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Systemic Investigation Identifying Salivary miR-196b as a Promising Biomarker for Early Detection of Head-Neck Cancer and Oral Precancer Lesions.

Cheng Ann-Joy AJ You Guo-Rung GR Lee Che-Jui CJ Lu Ya-Ching YC Tang Shang-Ju SJ Huang Yi-Fang YF Huang Yu-Chen YC Lee Li-Yu LY Fan Kang-Hsing KH Chen Yen-Chao YC Huang Shiang-Fu SF Chang Joseph Tung-Chieh JT

Diagnostics (Basel, Switzerland) 20210804 8

<h4>Background</h4>Liquid biopsy is a rapidly growing field, for it may provide a minimally invasive way to acquire pathological data for personalized medicine. This study developed a systemic strategy to discover an effective salivary biomarker for early detection of patients with head-neck squamous carcinoma (HNSC) and oral precancer lesion (OPC).<h4>Methods</h4>A total of 10 miRNAs were examined in parallel with multiple independent cohorts. These included a training set of salivary samples f ...[more]

PMID: 34441345

Similar Datasets

Project description:ObjectiveThe dysregulation of the human high-temperature requirement A (HtrA) family of serine proteases is associated with many malignancies. However, there are few reports on HtrAs in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the expression, prognostic value, and biological functions of HtrAs in HNSCC.MethodsThe RNA-sequencing data and clinical data of HNSCC were downloaded from The Cancer Genome Atlas (TCGA) database. The GSE30784 and GSE31056 datasets from the Gene Expression Omnibus (GEO) database were used for further verification. This study explored the differential expression of HtrAs and assessed their potential impact on the prognosis of HNSCC patients using a survival module. Correlations between clinical characteristics and HtrA expression levels were then explored using a Wilcoxon rank sum test. A Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed using "clusterProfile" in the R software. A Pearson/Spearman correlation test was applied to analyze the relationship between HtrAs and immune infiltration level/checkpoint genes. Validation of HtrA expression levels were carried out by RT-PCR and western blot in human squamous carcinoma cell lines (Fadu and Cal-27) and human non-tumorigenic bronchial epithelium cells (BEAS-2B). Finally, through cell transfection, CCK-8, Ki-67 immunofluorescence, and flow cytometry assays, the effect of HtrA3 knockdown on the malignant biological behavior of HNSCC cells was explored.ResultsThe gene expression levels of HtrAs were significantly upregulated and associated with patient age, TNM stage, clinical stage, and TP53 mutation status in the TCGA-HNSCC cohort. High expressions of HtrA1/3 were associated with shorter overall survival, shorter progress-free interval, and lower disease-specific survival in HNSCC. A nomogram for HtrAs was constructed and validated. HtrA-related genes were significantly enriched in the immune response and cell apoptosis pathway. In addition, the expression of HtrAs showed significant correlations with B cells, M cells, DC cell infiltration, and immune infiltration checkpoint (CD276, TNFRSF14). Validation of HtrA expression was carried out by RT-PCR and western blot. Results of in vitro experiments indicated that HtrA3 gene knockdown inhibits the proliferation of FaDu and Cal-27 cells while concurrently promoting apoptosis.ConclusionsHtrA3 shows significant potential as both a prognostic marker and a promising therapeutic target for HNSCC, highlighting its relevance and importance in future research and potential clinical applications.

Project description:Background: Circular RNAs (circRNAs) represent a newly identified class of non-coding RNAs that can be secreted into body fluids via exosomes and subsequently detected. While the function of circPRMT5 has been partially elucidated in certain tumor types, its role and underlying mechanisms in head and neck squamous cell carcinoma (HNSCC) remain inadequately understood. Furthermore, the diagnostic potential of circPRMT5 in saliva necessitates additional investigation.Methods: The expression of circPRMT5 was quantified using qRT-PCR. The biological function of circPRMT5 in HNSCC progression was confirmed both in vitro and in vivo. RNA sequencing (RNA-Seq) was used to find downstream targets for circPRMT5-IGF2BP3. IGF2BP3 and SERPINE1 expression levels were assessed using qRT-PCR, Western blotting, and immunohistochemistry. Additionally, the localization and interaction of circPRMT5, IGF2BP3 protein, and SERPINE1 in HNSCC were evaluated using RNA-FISH, immunofluorescence (IF), and RNA immunoprecipitation (RIP) assays. Ultimately, saliva exosomes were collected, identified and assessed using Western Blot, electron microscopy, particle size analysis and qRT-PCR.Results: Findings revealed that circPRMT5 was upregulated in HNSCC and promoted its proliferation and metastasis in vitro and in vivo. Mechanistically, circPRMT5 stabilized IGF2BP3 protein, which in turn stabilized SERPINE1 mRNA. Notably, the proliferative, invasive, and migratory effects of circPRMT5 in HNSCC were contingent upon the involvement of IGF2BP3 and SERPINE1. Furthermore, circPRMT5 levels were significantly elevated in the saliva of HNSCC patients, and positively correlated with increased lymph node metastasis and advanced T stage. These findings underscored the high diagnostic and predictive potential of circPRMT5 in HNSCC.Conclusions: CircPRMT5 plays a crucial role in promoting HNSCC proliferation and metastasis via the IGF2BP3-SERPINE1 pathway. It serves as a noninvasive diagnostic biomarker, indicating its potential as a valuable diagnostic and therapeutic target for HNSCC patients.

Dataset Information

Systemic Investigation Identifying Salivary miR-196b as a Promising Biomarker for Early Detection of Head-Neck Cancer and Oral Precancer Lesions.

Publications

Systemic Investigation Identifying Salivary miR-196b as a Promising Biomarker for Early Detection of Head-Neck Cancer and Oral Precancer Lesions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets